(peg in ESS a tide)
Treatment of anemia due to chronic kidney disease (CKD) in patients receiving dialysis
Note: Peginesatide is not indicated for use under the following conditions:
- CKD patients not receiving dialysis
- Cancer patients with anemia that is not due to CKD
- As a substitute for RBC transfusion in patients requiring immediate correction of anemia
Note: Peginesatide has not demonstrated improved symptoms, physical functioning, or health-related quality of life.
Serious hypersensitivity to peginesatide or any component of the formulation; uncontrolled hypertension
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Anemia associated with chronic kidney disease in patients receiving dialysis: IV, SubQ: Individualize dosing and use the lowest dose necessary to reduce the need for RBC transfusions.
Patients not currently receiving an erythropoiesis-stimulating agent (ESA) (initiate when hemoglobin is <10 g/dL): IV, SubQ: Initial dose: 0.04 mg/kg once monthly
Conversion from another ESA (epoetin or darbepoetin) to peginesatide:Note: The initial monthly peginesatide dose can be estimated based on the weekly dose of epoetin or darbepoetin at the time of substitution (see table); the same route of administration (SubQ or IV) of the previous ESA should be maintained after conversion to peginesatide. If previous ESA was epoetin, the first dose of peginesatide should be 1 week after the last epoetin dose. If previous ESA was darbepoetin, the first dose of peginesatide should be given in the place of darbepoetin at the next scheduled dose.
Conversion from Another ESA (Epoetin or Darbepoetin) to PeginesatidePrevious
Epoetin Alfa
Total WEEKLY Dose
(units/wk)
Previous
Darbepoetin Alfa
WEEKLY Dose
(mcg/wk)
Initial
Peginesatide
MONTHLY Dose
(mg/mo)
<2500
<12
2
2500 to <4300
12 to <18
3
4300 to <6500
18 to <25
4
6500 to <8900
25 to <35
5
8900 to <13,000
35 to <45
6
13,000 to <19,000
45 to <60
8
19,000 to <33,000
60 to <95
10
33,000 to <68,000
95 to <175
15
≥68,000
≥175
20
Table has been converted to the following text.
Conversion from Another ESA (Epoetin or Darbepoetin) to Peginesatide
Previous total weekly epoetin dose: <2500 units/wk
or
Previous weekly darbepoetin dose: <12 mcg/wk
then
Initiate peginesatide monthly dose at: 2 mg/mo
Previous total weekly epoetin dose: 2500 to <4300 units/wk
or
Previous weekly darbepoetin dose: 12 to <18 mcg/wk
then
Initiate peginesatide monthly dose at: 3 mg/mo
Previous total weekly epoetin dose: 4300 to <6500 units/wk
or
Previous weekly darbepoetin dose: 18 to <25 mcg/wk
then
Initiate peginesatide monthly dose at: 4 mg/mo
Previous total weekly epoetin dose: 6500 to <8900 units/wk
or
Previous weekly darbepoetin dose: 25 to <35 mcg/wk
then
Initiate peginesatide monthly dose at: 5 mg/mo
Previous total weekly epoetin dose: 8900 to <13,000 units/wk
or
Previous weekly darbepoetin dose: 35 to <45 mcg/wk
then
Initiate peginesatide monthly dose at: 6 mg/mo
Previous total weekly epoetin dose: 13,000 to <19,000 units/wk
or
Previous weekly darbepoetin dose: 45 to <60 mcg/wk
then
Initiate peginesatide monthly dose at: 8 mg/mo
Previous total weekly epoetin dose: 19,000 to <33,000 units/wk
or
Previous weekly darbepoetin dose: 60 to <95 mcg/wk
then
Initiate peginesatide monthly dose at: 10 mg/mo
Previous total weekly epoetin dose: 33,000 to <68,000 units/wk
or
Previous weekly darbepoetin dose: 95 to <175 mcg/wk
then
Initiate peginesatide monthly dose at: 15 mg/mo
Previous total weekly epoetin dose: ≥68,000 units/wk
or
Previous weekly darbepoetin dose: ≥175 mcg/wk
then
Initiate peginesatide monthly dose at: 20 mg/mo
Dosage adjustments:
If hemoglobin does not increase by >1 g/dL after 4 weeks: Increase dose by 25%; do not increase the dose more frequently than once every 4 weeks
If hemoglobin increases >1 g/dL in the 2-week period prior to the dose or >2 g/dL in 4 weeks: Reduce dose by 25% (or more) as needed to reduce rapid response
If hemoglobin approaches or exceeds 11 g/dL: Reduce or interrupt dose; after dose has been withheld and once the hemoglobin begins to decrease, may resume dose at ~25% below the previous dose
Inadequate or lack of response over a 12-week escalation period: Further increases are unlikely to improve response and may increase risks; use the minimum effective dose that will maintain a Hgb level sufficient to avoid RBC transfusions and evaluate patient for other causes of anemia. Discontinue therapy if responsiveness does not improve.
Missed doses: Administer a missed dose as soon as possible and restart peginesatide at the prescribed once monthly dosing frequency.
Refer to adult dosing.
No dosage adjustment provided in manufacturer 's labeling.
No dosage adjustment provided in manufacturer 's labeling (has not been studied).
Do not dilute prior to administration.
May be administered as an IV injection or SubQ injection. The IV route is generally used for hemodialysis patients; medication is injected via a special access port on the dialysis tubing during the dialysis procedure. Peritoneal dialysis patients should only administer therapy via the SubQ route. For SubQ injections, may inject in either the outer area of the upper arms, the front of the middle thighs, the abdomen (excluding the 2-inch area around the navel), or the upper outer buttocks area. Do not inject in skin that is tender, red, hard, scarred, or bruised.
Store refrigerated at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Protect from light. If necessary, may store at temperatures ≤25 ‚ °C (77 ‚ °F) for ≤30 days. After initial entry, store multidose vials at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); discard after 28 days.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Omontys: 10 mg/mL (1 mL [DSC]); 20 mg/2 mL (2 mL [DSC]) [contains phenol]
There are no known significant interactions.
Transferrin saturation and serum ferritin (prior to initiation and during therapy); hemoglobin (every 2 weeks after initiation and following dose adjustments until stable and sufficient to minimize need for RBC transfusion, then at least monthly following hemoglobin stability); blood pressure; seizures (following initiation for first few months, includes new-onset or change in seizure frequency or premonitory symptoms); allergic reaction; presence of antibodies (if common causes of lack or loss of response are ruled out)
>10%:
Cardiovascular: Hypotension (14%), hypertension (13%), procedural hypotension (11%)
Central nervous system: Headache (15%), fever (12%)
Endocrine & metabolic: Hyperkalemia (11%)
Gastrointestinal: Diarrhea (18%), nausea (17%), vomiting (15%)
Neuromuscular & skeletal: Muscle spasms (15%), arthralgia (11%), back pain (11%), extremity pain (11%)
Respiratory: Dyspnea (18%), cough (16%), upper respiratory tract infection (11%)
Miscellaneous: Arteriovenous fistula site complication (16%)
1% to 10%: Miscellaneous: Peginesatide-specific binding antibodies (1%)
<1% (Limited to important or life-threatening): Allergic reaction, infusion-related reactions, seizures
The pharmacokinetics are not altered based on population pharmacokinetic analyses.
The pharmacokinetics are not altered based on population pharmacokinetic analyses.
The pharmacokinetics are not altered based on population pharmacokinetic analyses.
Concerns related to adverse effects:
- Allergic reactions: Allergic reactions, including anaphylactic reactions, hypotension, bronchospasm, angioedema, and generalized pruritus, have been reported (rarely). Discontinue immediately and treat symptoms appropriately in patients who experience serious allergic/anaphylactic reactions.
- Lack/loss of response: Patients with a sudden loss of hemoglobin response should be evaluated for potential causes of decreased response (eg, iron deficiency, infection, bleeding, inflammation). If common causes are excluded, patient should be evaluated for the presence of peginesatide antibodies. During trials, peginesatide-specific binding antibodies were detected rarely (with a higher incidence noted in patients receiving subcutaneous compared to IV administration); however, no cases of pure red cell aplasia (PRCA) were observed in studies. Peginesatide is a synthetic, peptide-based erythropoiesis-stimulating agent (ESA) and cross-reactivity of the immune response against either endogenous or recombinant protein-based erythropoietin agents (eg, epoetin, darbepoetin) to peginesatide is unlikely due to the difference in amino acid sequence (Macdougall, 2011).
Disease-related concerns:
- Cancer patients: Clinical trials involving ESAs in cancer patients have shown an increased risk of death, MI, and stroke. Peginesatide is not indicated in cancer patients with anemia who do not have chronic kidney disease.
- Chronic kidney disease patients: [U.S. Boxed Warning]: An increased risk of death, serious cardiovascular events, and stroke were reported in chronic kidney disease (CKD) patients administered ESAs to target hemoglobin levels >11 g/dL; use the lowest dose sufficient to reduce the need for RBC transfusions. An optimal target hemoglobin level, dose, or dosing strategy to reduce these risks have not been identified in clinical trials. Hemoglobin rising >1 g/dL in a 2-week period may contribute to the risk (dosage reduction recommended). CKD patients who exhibit an inadequate hemoglobin response to ESA therapy may be at a higher risk for cardiovascular events and mortality compared to other patients. Adjustments in dialysis parameters may be needed after initiation of peginesatide. Patients treated with peginesatide may require increased heparinization during dialysis to prevent clotting of the extracorporeal circuit. Therapy is not appropriate for anemia treatment in CKD patients not receiving dialysis.
- Hypertension/cardiovascular disease: Use with caution in patients with a history of hypertension (contraindicated in uncontrolled hypertension) or cardiovascular disease (history or active) and stroke. Blood pressure should be controlled prior to start of (and during) therapy. Monitor closely throughout treatment; reduce or withhold peginesatide if blood pressure becomes difficult to control.
- Perisurgical patients: In clinical trials involving ESAs, an increased risk of death was observed in patients undergoing coronary artery bypass surgery (CABG) and an increased risk of deep vein thrombosis (DVT) was seen in those undergoing orthopedic procedures.
- Seizures: Have been observed in clinical studies with use; use with caution in patients with a history of seizures. Monitor closely for neurologic symptoms during the first several months of therapy.
- Severe anemia or acute blood loss: Due to the delayed onset of erythropoiesis, peginesatide is not recommended for acute correction of severe anemia or as a substitute for emergency transfusion.
Other warnings/precautions:
- Factors impairing erythropoiesis: Prior to treatment, correct or exclude deficiencies of iron, vitamin B12, and/or folate, as well as other factors which may impair erythropoiesis (inflammatory conditions, infections, bleeding).
- Iron supplementation: Prior to and periodically during therapy, iron stores must be evaluated. Supplemental iron is recommended if serum ferritin <100 mcg/L or serum transferrin saturation <20%. Most patients with CKD will require iron supplementation.
C
Adverse events were observed in animal reproduction studies with maternal exposure similar to that observed with human doses.
Peginesatide, a pegylated synthetic peptide, binds to the human erythropoietin receptor to induce erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells; induces the release of reticulocytes from the bone marrow into the bloodstream, where they mature to erythrocytes. There is a dose response relationship with this effect. This results in an increase in reticulocyte counts followed by a rise in hemoglobin levels.
IV: Dialysis patients: Vd: 34.9 mL/kg
SubQ: ~48 hours
IV: Healthy subjects: 25 hours, Dialysis patients: 47.9 hours; SubQ: Healthy patients: 53 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience hypo-/hypertension, hyperkalemia, headache, nausea, diarrhea, injection site irritation, arthralgia, or myalgia. Have patient report immediately to prescriber dyspnea, strength differences from one side to another, edema, or rash (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.